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Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
Hang Ji1,2, Guicheng Kuang1, Hailan Yang1
1Department of Neurosurgery, Sichuan University West China Hospital, Chengdu, China.
Frontiers in Cell and Developmental Biology
|March 26, 2025
Summary
Human and mouse cerebral aneurysm models show key differences in vascular smooth muscle cells, neutrophils, and macrophages. These findings highlight disparities and suggest optimizing the mouse model for better human relevance.
Area of Science:
- Biomedical research
- Genomics
- Vascular biology
Background:
- The mouse model is widely used for cerebral aneurysm (CA) research.
- However, its accuracy in reflecting human CA remains unclear.
Purpose of the Study:
- To investigate cellular and molecular differences between human and mouse CA models.
- To identify potential areas for improving the mouse model's human relevance.
Main Methods:
- Utilized single-cell RNA sequencing (scRNA-seq) data integration.
- Performed trajectory and gene regulatory network analyses.
- Employed uniform manifold approximation and projection (UMAP) for visualization.
Main Results:
- Discrepancies found in vascular smooth muscle cells (vSMCs), monocytes/macrophages, and neutrophils.
- Human vSMCs showed a fibroblast-like phenotype, unlike mouse vSMCs.
- Human CAs exhibited more acute inflammation and distinct neutrophil recruitment patterns (CXCL8) compared to mice (CCL).
- Macrophages in human unruptured CAs expressed higher M2 markers.
Conclusions:
- Identified subtle but significant disparities between human and mouse CA models.
- Findings may guide the optimization of the murine CA model for enhanced translational research.
